3-42874509-G-T

Position:

• chr3-42874509-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004391.3(CYP8B1):​c.1308C>A​(p.Gly436=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000623 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (0 hom.)
• Consequence: CYP8B1 NM_004391.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.33

Genes affected

CYP8B1 (HGNC:2653): (cytochrome P450 family 8 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum membrane protein catalyzes the conversion of 7 alpha-hydroxy-4-cholesten-3-one into 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one. The balance between these two steroids determines the relative amounts of cholic acid and chenodeoxycholic acid both of which are secreted in the bile and affect the solubility of cholesterol. This gene is unique among the cytochrome P450 genes in that it is intronless. [provided by RefSeq, Jul 2008]

(HGNC:):

ACKR2 (HGNC:1565): (atypical chemokine receptor 2) This gene encodes a beta chemokine receptor, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptor-mediated signal transduction are critical for the recruitment of effector immune cells to the inflammation site. This gene is expressed in a range of tissues and hemopoietic cells. The expression of this receptor in lymphatic endothelial cells and overexpression in vascular tumors suggested its function in chemokine-driven recirculation of leukocytes and possible chemokine effects on the development and growth of vascular tumors. This receptor appears to bind the majority of beta-chemokine family members; however, its specific function remains unknown. This gene is mapped to chromosome 3p21.3, a region that includes a cluster of chemokine receptor genes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-42874509-G-T is Benign according to our data. Variant chr3-42874509-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.33 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP8B1	NM_004391.3	c.1308C>A	p.Gly436=	synonymous_variant	1/1	ENST00000316161.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP8B1	ENST00000316161.6	c.1308C>A	p.Gly436=	synonymous_variant	1/1		NM_004391.3	P1

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152064 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000600 AC: 151 AN: 251488 Hom.: 0 AF XY: 0.000640 AC XY: 87 AN XY: 135916

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.000832

Gnomad NFE exome AF: 0.000844

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000640 AC: 935 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.000642 AC XY: 467 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.000730

Gnomad4 NFE exome AF: 0.000709

Gnomad4 OTH exome AF: 0.000580

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74402

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000400

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

CYP8B1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0090
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138292874; hg19: chr3-42916001;